Arthritis & rheumatology (Hoboken, N.J.)
October 20, 2026 · via Europe PMC
Single-cell analysis reveals CXCL16<sup>+</sup> dendritic cells and clonally expanded GZMK<sup>+</sup> CD4 T cells driving joint inflammation in psoriatic arthritis.
Mullins BJ, Shwetar J, Herrera A, +22 more, Koralov SB.
AI summary — for doctors, generated from the abstract only
In psoriatic arthritis joints, clonally expanded cytotoxic GZMK+ CD4 T cells appear to be recruited by CXCL16-producing dendritic cells.
What was studied
Multimodal single-cell sequencing of blood and synovial fluid from 6 PsA patients, compared with 1 RA patient and 6 healthy controls, with confirmation by flow cytometry and ELISA in 25 more PsA patients and 16 controls, and migration assays.
Key findings
- Synovial T cells showed activation and exhaustion-related markers, with clonally expanded GZMK+ CD4 cells carrying cytotoxic programs.
- Synovial dendritic cells expressed high CXCL16, and the CXCR6-CXCL16 and CXCR3-CXCL10 axes were implicated in recruitment and retention.
- PsA synovial T cells migrated more toward a CXCL16 gradient than paired blood cells.
Clinical relevance
It points to new potential targets in the PsA joint beyond IL-17 and IL-23.
Who should care
Limitations
Very small discovery cohort with only one RA comparator, and in vitro migration may not reflect in vivo behavior.
No clinical change; this is hypothesis-generating mechanistic work.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Objective
Psoriatic arthritis (PsA) is a chronic immune-mediated arthritis affecting approximately 30% of individuals with psoriasis. The mechanisms driving PsA joint inflammation remain incompletely defined.
Methods
To address this gap, we performed multimodal single-cell sequencing of immune cells from matched peripheral blood and synovial fluid (SF) from 6 PsA patients, with comparisons to a rheumatoid arthritis (RA) patient and 6 healthy controls (HC).
Results
SF CD4 and CD8 T cells displayed elevated expression of TOX, PDCD1, CTLA4, GZMK, CXCR3, and CXCR6, reflecting a tissue-specific activation state. CD4 T cell sub-clustering revealed clonally expanded populations enriched for GZMK and cytotoxic gene programs, suggesting antigen-driven activation. In contrast, CD8 T cell clonality showed a significant correlation with GZMK expression, however GZMK+ CD8 T cells in the joint exhibited a transcriptional signature consistent with functional exhaustion. Concurrently, SF was enriched for CD141+, CD1c+, CCR7+, and SIGLEC6+ dendritic cells (DCs), characterized by increased CXCL16 expression and antigen presentation pathways. Flow cytometry and ELISA in an additional 25 PsA patients and 16 HCs confirmed protein-level enrichment of key chemokines and GZMK+ T cells. Cell-cell communication analysis highlighted CXCR6-CXCL16 and CXCR3-CXCL10 chemokine axes as mediators of immune cell recruitment and retention, while in vitro assays showed enhanced migration of PsA SF T cells toward a CXCL16 gradient relative to paired blood.
Conclusion
Together, these findings suggest that clonally expanded GZMK+ CD4 T cells in PsA are cytotoxic and antigen-responsive, contributing to joint inflammation following recruitment by CXCL16-producing dendritic cells.
DOI
10.1002/art.70371
PMID
42901778
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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